Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An earlier, relatively small case-referent study has shown an increased risk for glassworks employees to die from stomach cancer, lung cancer, and cardiovascular disorders. This observation suggested an extended study virtually covering the entire glass-producing industry of Sweden. This new study confirmed the earlier results and, furthermore, an excess risk for colon cancer was also identified. No deviation was found in the cancer mortality pattern for all men in the glass-producing area compared to the whole of Sweden. The grouping of glassworks employees according to type of metal consumption at the glassworks showed the excess risks of stomach cancer, colon cancer, and cardiovascular deaths to relate to glassworks with a high consumption of lead, arsenic, antimony, and manganese. However, the strong correlation of these various metal exposures did not permit any successful separation of the effects of the different metals. For cardiovascular mortality, as for cancer, the glassblowers especially suffered from increased risk. Their exposure might, to a great extent, be oral, involving the glassblower's pipe as a "vector" for the exposure to various metals.
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PMID:Mortality in the Swedish glassworks industry. 343 43

Staurosporin, a broad-spectrum kinase inhibitor, induced cell spreading in a human colon cancer cell line, Colo 201. On collagen and laminin, cell spreading was induced in more than 90% of the cells and was dependent on very late activation antigen-3, as shown by an antibody inhibition assay. Cell spreading required divalent cations and showed the order of preference Mn2+ > Mg2+ > Ca2+. On fibronectin, only about 30% of the cells were observed to spread, and spreading occurred via a non-integrin, RGD-independent pathway. Staurosporin-induced spreading was inhibited by treatment with tyrosine kinase inhibitors herbimycin A and methyl 2,5-dihydroxycinnamate. Despite the presence of staurosporin, seven proteins (220, 175, 150, 98, 62, 58, and 45 kDa) showed increased levels of tyrosine phosphorylation in association with cell adhesion. Two of these (58 and 220 kDa) were identified by immunoprecipitation as Src product and tensin, respectively. Flow cytometric analysis showed that the Colo 201 cells expressed the alpha 2, alpha 3, alpha 6, and beta 1 chains of integrin, but expression of these chains was not influenced by staurosporin. Immunofluorescence microscopy revealed that the alpha 3 chain, diffusely expressed on the cell surface in the absence of staurosporin, was concentrated at focal adhesion plaques after staurosporin treatment. Neither alpha 2 nor alpha 6 was focalized by the treatment.
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PMID:Cell spreading in Colo 201 by staurosporin is alpha 3 beta 1 integrin-mediated with tyrosine phosphorylation of Src and tensin. 753 Jul 22

Free cytosolic [Ca2+] ([Ca2+]f) was measured at the single cell level using digitized video-intensified fluorescence microscopy and the fluorescent Ca2+ indicator, fura-2. Cells were irradiated at 1-4 Gy (dose rate of 6 Gy/min) with a 90Sr eye applicator mounted on the microscope. HeLa cells responding to ionizing radiation exhibited a maximal 3-4-fold transient rise in cytosolic and nuclear [Ca2+]f immediately upon irradiation, which persisted for at least 5 min before returning to baseline in most but not all cells. The radiation-induced rise in [Ca2+]f was blocked by 1 mM La3+, 100 nM nifedipine, or membrane potential depolarization, suggesting that HeLa cells possess a voltage-dependent Ca2+ channel that mediates the response to radiation. Experiments with Mn2+, a paramagnetic probe for extracellular Ca2+, showed that radiation stimulated an increase in Mn2+ influx, as witnessed by loss of fura-2 fluorescence. Thapsigargin and ryanodine, inhibitors of intracellular Ca2+ mobilization, also completely blocked the radiation effect, implying a linkage between the radiation-induced influx and mobilization of internal Ca2+ stores. Not all cells in an asynchronous culture responded identically to radiation. Upon synchronization with thymidine/aphidicolin, cells in the S- and G2/M-phase exhibited radiation-induced changes in [Ca2+]f, whereas G1-phase cells did not. In addition, the increased [Ca2+]f of irradiated G2/M phase cells did not fully return to pretreatment levels. Further studies utilizing MDA-MB-231 and MCF-7 human breast and HT-29 human colon cancer cell lines indicate that radiation can alter Ca2+ homeostasis in other epithelial cell types. In the case of MDA-MB-231 and HT-29 cells, oscillations in cytosolic [Ca2+]f levels were observed that persisted for up to 50 min. The kinetics and inhibitor sensitivities differed from HeLa cells, indicating a different type of mechanism for the radiation effects on cell [Ca2+]f. Survival studies with HeLa and MDA-MB-231 cells did not reveal a connection between the radiation effects on cellular Ca2+ homeostasis and cell survival.
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PMID:Ionizing radiation induces a transient increase in cytosolic free [Ca2+] in human epithelial tumor cells. 792 44

A population-based case-control study including 726 patients with colon cancer, 575 with rectum cancer, and 1400 population controls matched on age (+/- 5 yrs.) and sex was carried out to evaluate the association of ten inorganic elements, including potassium, sodium, calcium, magnesium, iron, manganese, zinc, copper, phosphorus and selenium, and other dietary factors with colorectal cancer. Single variable analysis adjusted for age and sex showed most of the ten elements, except sodium and selenium, may reduce the risk of the development of colorectal cancer. Correlation analysis indicated these eight elements correlated closely to the "vegetable factors", e.g., dietary fibre, and so on, since the major sources (about 80%) of these elements were from vegetables. Multi-variable logistic regression analysis showed nine elements (except sodium) may confound the effects of some dietary factors (such as dietary fibre and vitamin C) on the occurrence of colorectal cancer and only contribute to it. The results showed a close association between saturated fatty acid, mono-unsaturated fatty acid, dietary fibre, vitamins C and E, and colorectal cancer.
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PMID:[Relationship between colorectal cancer and ten inorganic elements]. 813 59

In the art glass industry workers run increased risks of dying from several types of cancer, cardiovascular diseases, and cerebrovascular diseases. This paper considers the diseases of glass workers in relation to exposure to particular elements, a high degree of correlation being found for some of them. Case-referent evaluations showed an association between stomach cancer and exposure to a mixture of elements, namely, arsenic, copper, nickel, and manganese, and to some extent also to lead and chromium. For colon cancer, a clearly increasing trend in risk was seen with increasing use of antimony, and to some extent also with increasing use of lead, the two elements being strongly correlated. For lung cancer no obvious correlation with any metal could be found. In addition, the risk for death from cardiovascular disease was fairly evenly distributed, although slightly more related to increasing consumption of the strongly correlated metals nickel and copper.
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PMID:Epidemiologic studies of occupational cancer as related to complex mixtures of trace elements in the art glass industry. 815 83

Binding of colon cancer to extracellular matrix (ECM) proteins and mesenchymal cells that comprise the basement membrane is important in migration and metastasis. This study defines the conditions and surface structures necessary for adhesion of HT-29 cells to ECM proteins and cell monolayers. Binding began within minutes and peaked by 1 hr, with 80-95% of HT-29 cells binding to the ECM proteins, collagen IV, laminin, fibronectin, and vitronectin and 40-75% binding to monolayers of fibroblasts, smooth muscle cells, and HT-29 cells. Treating mesenchymal cells with the fibrogenic cytokines, IL-1, IL-4, or TNF-alpha, which increase production of ECM proteins, did not alter binding of HT-29 cells to these monolayers. Attachment of HT-29 cells to cell monolayers was inhibited by cytochalasin D and sodium azide, but not cycloheximide or neuraminidase. Attachment to ECM proteins, in contrast, was unaffected by any of these metabolic inhibitors but required certain divalent cations (Mg2+ and Mn2+ but not Ca2+). Antibody to the integrin beta 1, chain (CD29) eliminated binding to collagen and laminin but not to fibronectin, fibroblasts, and HT-29 monolayers. Antibody to the vitronectin receptor inhibited binding to fibronectin. Antibodies to integrin alpha 1-alpha 6 chains had no effect on any adhesion event. Three colon cancer cell lines were tested for expression of VLA antigens: alpha 2 and alpha 3 were detected on all three, alpha 1 and alpha 6 were variably expressed, while alpha 4 and alpha 5 were absent. This study demonstrates that several mechanisms account for tumor cell attachment to substratum and cells.
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PMID:Mechanisms of colon cancer binding to substratum and cells. 876 78

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known to decrease manganese superoxide dismutase (MnSOD) activity in colonic mucosa. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is absent or decreased in most tumours, including those from the colon. This study was designed to determine the effects of high dietary lipid and iron levels on MnSOD activity during the early weeks of colon carcinogenesis. Male Fischer-344 rats were fed 20% lipid diets of either corn oil or menhaden oil containing adequate iron (35 mg/kg) or supplemental iron (535 mg/kg). Rats from each diet were divided into carcinogen treatment groups and given two weekly injections of either azoxymethane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collected 1, 6 and 12 wk following injections and analysed for MnSOD activity, mineral concentration and nuclear aberrations. Results showed that iron supplementation increased nuclear aberrations, and decreased manganese concentration and MnSOD activity in colonic mucosa ot control animals. AOM, and interaction of iron and AOM, also decreased MnSOD activity. A decrease in the activity of this enzyme during carcinogenesis may be one mechanism whereby these dietary factors ultimately increase tumour risk.
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PMID:Decrease of manganese superoxide dismutase activity in rats fed high levels of iron during colon carcinogenesis. 973 29

Aberrant crypt foci (ACF) are preneoplastic lesions for colon cancer. Altered amounts of copper-zinc (CuZnSOD) and manganese (MnSOD) superoxide dismutases have been implicated in multistage carcinogesis of both rodents and humans. Dietary factors are potential modulators of both CuZnSOD and MnSOD activity. The purpose of this study was to investigate the interactive effects of dietary copper, manganese, and iron on 3,2'-dimethyl-4-aminobiphenyl (DMABP)-induced ACF and superoxide dismutase activities in weanling rats fed low or adequate copper (0.8 or 5.1 microg Cu/g diet), low or adequate manganese (0.6 or 17 microg Mn/g diet), and adequate or high iron (37 or 140 microg Fe/g diet). Twelve rats were allowed free access to each of these eight diets for 3.5 wk prior to DMABP administration and for an additional 8 wk after the first DMABP injection. Rats fed low dietary copper had 105% (P < 0.0001) higher formation of DMABP-induced ACF than those fed adequate dietary copper. Rats ingesting low rather than adequate dietary manganese had 23% higher formation of ACF, and rats ingesting high rather than adequate dietary iron had 18% higher formation of ACF. Heart total superoxide dismutase activity was significantly correlated with the number of ACF (r = -0.43, P < 0.0001) in rats administered DMABP. These results suggest that dietary alterations that affect superoxide dismutase activity may affect cancer susceptibility.
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PMID:Dietary copper, manganese and iron affect the formation of aberrant crypts in colon of rats administered 3,2'-dimethyl-4-aminobiphenyl. 1022

We found earlier in human breast and colon tumors, an augmented level of Gal : 3-O-sulfotransferase activities showing, respectively, an acceptor preference to blood group T-hapten (Group A enzymes) or Galbeta1,4GlcNAc (Group B enzymes) on the mucin Core 2 structure [Chandrasekaran EV, Jain RK, Vig R, and Matta KL (1997) Glycobiology 7: 753-68]. The present study reports these enzyme activities in human tumor cell lines and additional tumor specimens. The human colon tumor epithelial cell lines, akin to their parent tumors, express Group B enzyme activity. The acceptor specificity and kinetic properties, such as divalent metal ion activation and pH dependent activity profile, of the colon cancer line LS180 enzyme activity are identical to those of colon tissue specimens. Consistent with breast tumor specimens, the Group A enzyme activity is present in human breast tumor epithelial cell lines, with some exceptions. The Gal : 3-O-sulfotransferases show specific binding to Aleuria aurantia lectin, suggesting the presence of asparagine linked carbohydrate chains containing an inner core alpha1,6-fucosyl residue on these enzymes. Calf lymph nodes contain GlcNAc : 6-O-sulfotransferase as well as Group A Gal : 3-O-sulfotransferase activities, which differ in pH dependent profiles, pH optima (7.6 and 7.0, respectively) and the influence of Mn2+.
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PMID:Characterization of distinct Gal:3-O-sulfotransferase activities in human tumor epithelial cell lines and of calf lymph node GlcNAc : 6-O-sulfotransferase activity. 1081 89

We studied the effects of Ukrain, a novel antitumor drug, on the activities of calcium, magnesium-dependent endonuclease (CME) and manganese-dependent endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting effect on both CME and MnDE, similar to that exerted by erythropoietin, which was used as a reference preparation. Both Ukrain and erythropoietin also caused dose-dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME activity in the nuclei of the lymphocytes of colon cancer patients was differential, depending on treatment efficacy. The results suggest that DNA-nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.
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PMID:Effects of Ukrain on the activities of DNA-nicking enzymes. 1134 37


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